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Multiple roles for integrins in Drosophila glial development

University of British Columbia

Glia are well known for providing essential physical and metabolic support to neurons, as well as regulating neuronal development. Glial development is also modulated by external signals from other cells and the extracellular matrix (ECM). Many signals are transduced into glia by specific receptors, such as integrins for the ECM. Previous studies show that integrins are expressed by all major vertebrate glial subtypes and play key roles in many important developmental processes. However complex composition of the integrin family and difficulties of manipulating genes in vertebrates limit the understanding of in vivo functions of integrins in glia. Drosophila melanogaster is an excellent model for genetic analysis of the nervous system development. In this dissertation, I investigated integrin function in Drosophila glia. Integrins are expressed by glia in both the central and peripheral nervous systems at larval stages, where they form complexes with Talin and Integrin-Linked-Kinase (ILK). I found that integrin complexes were localized to different glia layers in the larval peripheral nerve and optic stalk. By using MARCM and RNA interference techniques, I found that integrins are required for multiple developmental events in individual and populated glia. In the peripheral nerve, integrins are important for glial ensheathment. When integrins were removed, perineurial glia failed to initiate or maintain their wrapping around the nerve and wrapping glia failed to send out numerous membrane processes between axons. In the optic stalk, integrins were necessary for glial migration, deposition and barrier formation. Removal of integrins impaired glial migration into the eye disc. Moreover, perineurial glia tended to aggregate at the anterior half and form multiple layers, and carpet glia failed to form organized septate junctions along the optic stalk. These glial defects resulted in photoreceptor axonal stalling in the eye disc and optic stalk, and mis-targeting in the brain. My work suggests that integrins are important for different aspects of Drosophila glial development and reveals a new glial function in helping photoreceptor axons through the optic stalk. Integrin distribution implicated that integrins may mediate glia-glia or glia-neuron interactions through ECM and non-ECM ligands.

Text

2012-07-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/42838

Zoology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/